Dr Grania Brigden TB Symposium, Yerevan 2015.

3P TB R&D Proposal

Push, Pull, Pool.

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New treatments and approaches to Tuberculosis Tuberculosis Symposium – Eastern Europe and Central Asia

RA Ministry of Health and Médecins Sans Frontières

MDR-TB treatment

The issues

Old – ‘newest’ drug in current regimens was introduced 50 years ago

Long – Treatment takes two years

Complex – different treatment regimens for individual resistance patterns; about 5 different drugs (14,000 pills), including 8 months of painful injections

Toxic – extreme side effects include deafness, psychosis, constant nausea and vomiting, hallucinations, weight loss and more

Expensive – Can cost up to $5000 in drug costs alone

Inadequate – high default rates and low cure rates (~50% for MDR-TB, 13% for XDR-TB) contribute to further resistance; no paediatric formulations

Unproven – No randomized clinical trials conducted or planned for the current regimen

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TB drug regimen R&D

Clear case of market failure

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Healthy Pipeline?

Hepatitis C

Phase I over 15 Phase II 14 Phase III 11

Total: over 40!

TB

Phase I 0 Phase II 5 Phase III 1

Total: 6

NCEs in Clinical Development:

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• Two new drugs...no new regimens. Limited

data on how to use them together

• New drugs registered but not available

• High prices; no price transparency

• Chronic under investment in TB R&D

• Likely “famine period” for new TB drugs

ahead

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Market Failure leading to…

Annual Global Plan Research Funding

Targets versus 2013 Funding

$600,000,000

$800,000,000

$400,000,000

$200,000,000

$0

Basic Science New Diagnostics New Drugs Operational

Research New Vaccines

$80,000,000

$71,754,311 $95,172,788

$380,000,000

$255,428,811

$740,000,000

$137,658,205

$420,000,000

Global Plan Annual Targets 2013 Funding

$340,000,000

$67,771,567

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Funders under 2%

$28,976,179

(11%)

Company X

$11,640,556

(5%)

CDC

$7,970,437

(3%)

Otsuka Pharmaceuticals

$58,717,259

(23%)

USAID

$8,748,00

(3%)

EDCTP

$12,494,787

(5%)

Gates Foundation

$86,696,528

(27%)

NIH Other ICs

$7,074,534

(3%)

NIH NIAID

$34,680,504

(14%)

DFID

$9,885,460

(4%)

European

Commission

$6,544,567

(2%)

2013 Funding for New

TB Drugs: $255,428,811

TB Drug R&D: a Charitable Endeavor?

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• Private sector decreased TB drug R&D from 2012- 2013

• US government funding flat-lining

• Pfizer withdrew from anti-infectives

• AstraZeneca withdrew from NTDs, TB & Malaria

• Otsuka decreased drug discovery efforts, contribution may further decline after development of delaminid is completed

• Similar situation may occur with J&J and bedaquiline

• Pipeline gap in phase I

• Early-stage & preclinical research- public institutions, small companies or PDPs, do they have the capital or capacity for clinical trials?

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Where is the investment?

How do we plug the gap in the funding needs and

prevent the flight of private sector investment?

A mix of incentives & the collective management of IP:

– Push funding to finance R&D activities upfront (i.e.

through grants)

– Pull funding to incentivise R&D activities through the

promise of financial rewards on the achievement of

certain R&D objectives (i.e. through milestone prizes)

– Pooling of intellectual property (IP) to ensure open

collaborative research and fair licensing for

competitive production of the final products

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3Ps: Push + Pull + Pool

Open Collaborative Framework*

Scientific Data

Clinical Study Results

Compound Libraries

Patents & IP on drugs & other technologies

Enabled through Intellectual Property &

data pooling

Results from

scientific studies

& data

Candidate drugs /

Other technology

* Potentially a virtual model, where

different elements are housed in

different existing institutions with

overall coordination

Legal right to use

data, combine,

manufacture and

sell products

Results from all

studies are

published

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Open collaborative model

Hit to Lead Lead Opt. Pre-clinical

Studies GLP Tox Phase I Phase II Phase III

Milestone

Prize (Size 3)

for

combination

regimen

successfully

completing

Phase II

Milestone Prize

(Size 2) for

entering clinical

development

(Phase I)

Grant funding

for studies

from the fund

Grant funding for

Phase III from

existing and new

sources

Milestone Prizes

Grant funding

Legend

Various TB Compounds

Indicates Combination

Small, early-stage Milestone Prize (Size 1)

mix of small financial and recognition

prizes) for licensing the compound to the

Open Collaborative Framework

Clinical Development Later Stage Preclinical Discovery

Open collaborative model

– transforms drug pipeline

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This framework offers four benefits over the current

system:

1) reduces the duplication of research efforts thereby

saving time and money

2) “de-risks” potential combinations as early and as

affordably as possible

3) accelerates drug combination development

4) reduces the risk of resistance to new compounds

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Benefits of 3P over current

model

Relevance to Eastern Europe?

• High burden of MDR/XDR TB

• Graduating out of GF/Donor funding

• R&D increasingly on the agenda of high level meetings

eg Riga meeting, March 2014 and possibly Eastern

Partnership summit

• Widespread political support required; Ministers

attending these meetings need to support this initiative.

• Strengthen in-country academic institutes, scientific

communities and clinical trial sites.

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Thanks!

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